Biochemical and structural characterization of the DNA-binding properties of human TRIP4 ASCH domain reveals insights into its functional role.

TRIP4 is a conserved transcriptional coactivator that is involved in the regulation of the expression of multiple genes. It consists of a classical N-terminal C2HC5-like zinc-finger domain and a conserved C-terminal ASCH domain. Here, we characterized the DNA-binding properties of the human TRIP4 ASCH domain. Our biochemical data show that TRIP4-ASCH has comparable binding affinities toward ssDNA and dsDNA of different lengths, sequences, and structures. The crystal structures reveal that TRIP4-ASCH binds to DNA substrates in a sequence-independent manner through two adjacent positively charged surface patches: one binds to the 5'-end of DNA, and the other binds to the 3'-end of DNA. Further mutagenesis experiments and binding assays confirm the functional roles of key residues involved in DNA binding. In summary, our data demonstrate that TRIP4-ASCH binds to the 5' and 3'-ends of DNA in a sequence-independent manner, which will facilitate further studies of the biological function of TRIP4.

High-Temperature Protonic Conduction in La2 NiO4+ δ -Based Ruddlesden-Popper Type Oxides: Correlation with Concentration of Interstitial Oxide Ions.

Oxygen-excess La2 NiO4+ δ (LNO) conducts oxide ions, electron holes, and hydroxide ions simultaneously on exposing to wet oxygen, exhibiting the potential as a cathode material in protonic ceramic fuel cells. Since the incorporation of protons in oxygen-excess LNO is via the hydration reaction assisted by interstitial oxide ions, in this work, the concentration of interstitial oxide ions is reduced and increased by substituting Ni with Cu and Co, respectively. A higher concentration of interstitial oxide ions leads to a high proton concentration, indicating the predominant role of interstitial oxide ions in the hydration reaction, different from that in the oxygen-deficient oxides, where protons are introduced by dissociative absorption of water molecules by oxygen vacancies. The theoretical calculation indicates that protons in Co-doped LNO prefer to locate between the interstitial oxide ions and unshared apical oxide ions. A trapping effect is found between protons and the oxide ions near Cu, leading to decreased proton mobility. Protonic conductivity at 400-575 °C is then directly measured by a Hebb-Wagner direct current polarization method with La0.99 Ca0.01 NbO4- δ as the blocking electrode, enabling the observation that Co-doped LNO has the highest protonic conductivity among the samples studied in this work.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Frequency suppression of director oscillations in AC-driven liquid-crystal-based terahertz phase shifters.

Frequency-induced instability is widely present in nematic liquid crystals (LCs), which poses a problem in improving liquid-crystal-based phase-shift devices driven by alternating currents. Herein, the Fréedericksz transition of thick nematic LCs was investigated under alternating electric fields to reveal the suppression of frequency-induced instability in the low frequency range. By extending the Frank-Leslie equation to the AC-driven case, the response of the LC was numerically calculated, and the frequency threshold for suppressing the driven instability was estimated in conjunction with the perturbation method. Experimentally, the frequency suppression of LC fluctuations was verified by using applied electric fields. In addition, the root-mean-square-error of the refractive index was measured to be less than 2 × 10-5, which excludes the convective instability-generating domains in devices. It was revealed that the fabricated thick LC phase shifters provided a phase shift of more than 360° at 2 THz and can be used in the terahertz band. It was observed that the electrically driven phase-shift characteristics were in accordance with the theoretical results as the threshold frequency condition was satisfied. This work provides an experimental and theoretical reference for improving modulation performance and enhancing the characterization of AC-driven LC-based phase-shift devices.

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.

Importance: Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones. Objective: To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones. Design, Setting, and Participants: This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics. Genetic proxies of thiazide diuretics were derived from the International Consortium for Blood Pressure. Kidney stone cases and controls were derived from the Million Veteran Program, UK Biobank, and the FinnGen study. These cross-sectional designs do not report a duration of follow-up. Data analysis was performed in May 2023. Exposure: Genetic proxies of thiazide diuretics were genetic variants in the thiazide-sensitive sodium chloride cotransporter gene associated with systolic blood pressure. Genetic proxies of ß-blockers and systolic blood pressure served as negative controls. Main Outcomes and Measures: The main outcome was the odds of kidney stones. The secondary outcomes were serum laboratory values relevant to the treatment of kidney stones. Results: The main analysis included up to 1 079 657 individuals, including 50 832 kidney stone cases and 1 028 825 controls. In a meta-analysis of all cohorts, genetic proxies of thiazide diuretics were associated with a lower odds of kidney stones (OR, 0.85; 95% CI, 0.81-0.89; P < .001). Genetic proxies of ß-blockers (OR, 1.02; 95% CI, 0.96-1.07; P = .52) and systolic blood pressure (OR, 1.00; 95% CI, 1.00-1.01; P = .49) were not associated with kidney stones. Genetic proxies of thiazide diuretics were associated with higher serum calcium (ß [SE], 0.051 [0.0092]; P < .001) and total cholesterol (ß [SE], 0.065 [0.015]; P < .001), but lower serum potassium (ß [SE], -0.073 [0.022]; P < .001). Conclusions and Relevance: In this genetic association study, genetic proxies of thiazide diuretics were associated with reduced kidney stone risk. This finding reflects a drug effect over the course of a lifetime, unconstrained by the limited follow-up period of clinical trials.

Longitudinally variable 3D optical polarization structures.

Generation and manipulation of three-dimensional (3D) optical polarization structures have received considerable interest because of their distinctive optical features and potential applications. However, the realization of multiple 3D polarization structures in a queue along the light propagation direction has not yet been reported. We propose and experimentally demonstrate a metalens to create longitudinally variable 3D polarization knots. A single metalens can simultaneously generate three distinct 3D polarization knots, which are indirectly validated with a rotating polarizer. The 3D polarization profiles are dynamically modulated by manipulating the linear polarization direction of the incident light. We further showcase the 3D image steganography with the generated 3D polarization structures. The ultrathin nature of metasurfaces and unique properties of the developed metalenses hold promise for lightweight polarization systems applicable to areas such as 3D image steganography and virtual reality.

Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.

Interferon regulatory factor 4 (IRF4) is a transcription factor that regulates the development and function of immune cells. Recently, a new multimorphic mutation T95R was identified in the IRF4 DNA-binding domain (DBD) in patients with autosomal dominant combined immune deficiency. Here, we characterized the interactions of the wild-type IRF4-DBD (IRF4-DBDWT) and T95R mutant (IRF4-DBDT95R) with a canonical DNA sequence and several noncanonical DNA sequences. We found that compared to IRF4-DBDWT, IRF4-DBDT95R exhibits higher binding affinities for both canonical and noncanonical DNAs, with the highest preference for the noncanonical GATA sequence. The crystal structures of IRF4-DBDWT in complex with the GATA sequence and IRF4-DBDT95R in complexes with both canonical and noncanonical DNAs were determined, showing that the T95R mutation enhances the interactions of IRF4-DBDT95R with the canonical and noncanonical DNAs to achieve higher affinity and specificity. Collectively, our data provide the molecular basis for the gain-of-function and new function of IRF4T95R.

Multifunctional transmission polarization conversion metasurface based on dislocation-induced anisotropy at the terahertz frequency.

Manipulating the polarization state of terahertz waves is critical for terahertz communication systems. This study proposes a terahertz band polarization conversion metasurface based on dislocation-induced anisotropy. Numerical simulation results revealed that the polarization conversion of orthogonal linearly polarized light, orthogonal circularly polarized light, linearly polarized light to circularly polarized light, and circularly polarized light to linearly polarized light can be realized. Furthermore, the simulation revealed that multifunctional polarization conversion could be achieved by various structures of the bilayer metasurface. Thus, the proposed design can be generalized. The proposed metasurface exhibits considerable potential for applications in terahertz communications.

Partial Sulphidation to Regulate Coordination Structure of Single Nickel Atoms on Graphitic Carbon Nitride for Efficient Solar H2 Evolution.

To develop a non-precious highly efficient cocatalyst to replace Pt on graphitic carbon nitride (g-C3 N4 ) for solar H2 production is great significant, but still remains a huge challenge. The emerging single-atom catalyst presents a promising strategy for developing highly efficient non-precious cocatalyst owing to its unique adjustability of local coordination environment and electronic structure. Herein, this work presents a facile approach to achieve single Ni sites (Ni1 -N2 S) with unique local coordination structure featuring one Ni atom coordinated with two nitrogen atoms and one sulfur atom, confirmed by high-angle annular dark-field scanning transmission electron microscopy, X-ray absorption spectroscopy, and density functional theory calculation. Thanks to the unique electron structure of Ni1 -N2 S sites, the 1095 µmol g-1 h-1 of high H2 evolution rate with 4.1% of apparent quantum yield at 420 nm are achieved. This work paves a pathway for designing a highly efficient non-precious transition metal cocatalyst for photocatalytic H2 evolution.

Cognitive Outcomes in the Pragmatic Investigation of optimaL Oxygen Targets (CO-PILOT) trial: protocol and statistical analysis plan.

INTRODUCTION: Long-term cognitive impairment is one of the most common complications of critical illness among survivors who receive mechanical ventilation. Recommended oxygen targets during mechanical ventilation vary among international guidelines. Different oxygen targets during mechanical ventilation have the potential to alter long-term cognitive function due to cerebral hypoxemia or hyperoxemia. Whether higher, intermediate or lower SpO2 targets are associated with better cognitive function at 12-month follow-up is unknown. METHODS AND ANALYSIS: The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is an ongoing pragmatic, cluster-randomised, cluster-crossover trial comparing the effect of a higher SpO2 target (target 98%, goal range 96%-100%), an intermediate SpO2 target (target 94%, goal range 92%-96%) and a lower SpO2 target (target 90%, goal range 88%-92%) on clinical outcomes in mechanically ventilated patients admitted to the medical intensive care unit at a single centre in the USA. For this ancillary study of long-term Cognitive Outcomes (CO-PILOT), survivors of critical illness who are in the PILOT trial and who do not meet exclusion criteria for CO-PILOT are approached for consent. The anticipated number of patients for whom assessment of long-term cognition will be performed in CO-PILOT is 612 patients over 36 months of enrolment. Cognitive, functional and quality of life assessments are assessed via telephone interview at approximately 12 months after enrolment in PILOT. The primary outcome of CO-PILOT is the telephone version of the Montreal Cognitive Assessment. A subset of patients will also complete a comprehensive neuropsychological telephone battery to better characterise the cognitive domains affected. ETHICS AND DISSEMINATION: The CO-PILOT ancillary study was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Molecular mechanism of S-adenosylmethionine sensing by SAMTOR in mTORC1 signaling.

The mechanistic target of rapamycin-mLST8-raptor complex (mTORC1) functions as a central regulator of cell growth and metabolism in response to changes in nutrient signals such as amino acids. SAMTOR is an S-adenosylmethionine (SAM) sensor, which regulates the mTORC1 activity through its interaction with the GTPase-activating protein activity toward Rags-1 (GATOR1)-KPTN, ITFG2, C12orf66 and SZT2-containing regulator (KICSTOR) complex. In this work, we report the crystal structures of Drosophila melanogaster SAMTOR in apo form and in complex with SAM. SAMTOR comprises an N-terminal helical domain and a C-terminal SAM-dependent methyltransferase (MTase) domain. The MTase domain contains the SAM-binding site and the potential GATOR1-KICSTOR-binding site. The helical domain functions as a molecular switch, which undergoes conformational change upon SAM binding and thereby modulates the interaction of SAMTOR with GATOR1-KICSTOR. The functional roles of the key residues and the helical domain are validated by functional assays. Our structural and functional data together reveal the molecular mechanism of the SAM sensing of SAMTOR and its functional role in mTORC1 signaling.

Electronically controlled flexible terahertz metasurface based on the loss modulation of strontium titanate.

A flexible terahertz metamaterial is designed to control the transmittance through an external electric field. Two different metallic structures, the split ring (type I structure) and the split ring inside a ring (type II structure), were prepared and voltage was applied through a forked finger electrode. The structures were wrapped in a thin film made by mixing strontium titanate nanopowder with polyimide in a certain ratio. Under normal incidence, the transmittance is controlled by applying a voltage to adjust the imaginary part of the permittivity of strontium titanate. The modulation depth of the type I structure at 1.08 THz is 40.1%, and that of the type II structure at 1.16 THz is 44.7%. The working bandwidths of the two structures are 0.07 THz and 0.42 THz, respectively, and are greatly broadened by combining with the ring. The proposed design enriches the modulation method of the transmission of metamaterials and broadens the application range of flexible terahertz metasurfaces.

Coaxial double-hole PEDOT: PSS electrodes achieving tunable terahertz zoomable convergence.

The local wavefront modulation technique in the terahertz band is an important basis for the development of terahertz modulation technology. Here, an electrically controlled convergent tunable device based on patterned transparent electrode poly (3, 4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT: PSS) is realized to locally tune the terahertz wavefront. The device consists of two substrates with circular-hole electrodes and liquid crystal sandwiched between them. The refractive index gradient of liquid crystal in the device can be generated by the coaxial double-hole electrodes, which realize continuous control of significant focusing of the terahertz wave. The test results show that the focal length can be modulated in the range of 3-12 cm with varied external voltage; when it varies from 3 to 8 V, the 1/e2 radius of the spot decreases to 1.3 mm, 0.27 times the initial state, and the spot central intensity magnification increases gradually with the change, up to 3.31 times. The acquisition of the large tunable focal length range of the continuous terahertz zoom device shows that the construction of the gradient refractive index is an important method to regulate the terahertz wavefront by optical means, which greatly promotes the research of terahertz imaging devices.

The Effect of Hyperbaric Oxygen on Bone Healing Efficiency After Maxillary Sinus Lateral Augmentation Using Xenograft: An In Vivo Pilot Study on Histomorphometric Analysis.

It was hypothesized that hyperbaric oxygen (HBO) could increase bone healing efficiency according to a protocol with a special window of healing time when maxillary sinus lateral augmentation is performed with only xenograft. The histomorphometric efficiency of HBO on the maxillary sinus lateral augmentation was examined by designing five different in vivo healing periods. Five patients receiving maxillary sinus lateral augmentation with xenograft each received a different treatment healing protocol: 6 weeks natural healing (control [Ctl]), 5 weeks with HBO (T1), 6 weeks with HBO (T2), 9 weeks with HBO (T3), and 13 months natural healing (TM). Biopsy samples were harvested, and quantitative histomorphometric analysis was performed regarding key factors BMP-2 and RUNX2. Analysis of variance and Tukey test were used for pairwise comparisons. Time-dependent relationships of the factors' expression densities were conducted using quadratic regression fitting. There were statistically significant differences among the groups, except for T2/T3 and T2/TM for BMP-2 and for T2/T3 and TM/Ctl for RUNX2. Both BMP-2 and RUNX2 showed quadratic trends, presenting an initial upward trend and eventually a downward trend depending on T1, T2, and T3 groups. Early stimulation, achieved by keeping HBO until 6 to 9 weeks after maxillary sinus lateral augmentation with xenograft, seemed to be the time window that benefitted bone healing efficiency the most.

Active polarization-independent plasmon-induced transparency metasurface with suppressed magnetic attenuation.

A tunable polarization-independent plasmon-induced transparency (PIT) metasurface based on connected half-ring and split-ring resonators is proposed to working in the terahertz band. We analyze the PIT effect in metasurfaces comprising of ring resonator and split ring resonator. Due to the magnetic attenuation caused by the reverse current between the two resonators, the relative position of the ring resonator and the split-ring resonator greatly affects the strength of the PIT effect. Magnetic attenuation weakens the dark mode of the split ring resonator. Through simulation and experiment, it is found that connecting the ring resonator and split-ring resonator can avoid magnetic attenuation and achieve a stronger PIT window. Furthermore, the fourfold rotation structure of the connected half-ring and split-ring resonator on silicon substrate achieves an optically controlled polarization-independent PIT effect. The design would provide significant guidance in multifunctional active devices, such as modulators and switches in terahertz communication.

Efficient terahertz polarization conversion with hybrid coupling of chiral metamaterial.

We propose an ultrathin terahertz waveplate of bi-layer chiral metamaterial for cross-polarization conversion at asymmetric transmission. The chiral metamaterial is constructed with hybrid coupling plasmonic resonators of a concentric ring and a double-split ring. The terahertz metamaterial can efficiently convert the ${y}$y-polarized wave into the ${x}$x-polarized wave with the cross-polarized transmittance over 97% and the polarization conversion ratio of 99% in simulation. The asymmetric transmission parameter, defined by the difference between two opposite propagating transmittances, can be as high as 0.9. The operation frequency and efficiency are geometrically adjustable with the ring size by exploiting the hybrid coupling effect of electric and magnetic resonances. The presented metamaterial enables the functionality of the nonreciprocal terahertz waveplate with high isolation.

Inhibition of Autophagy via Lysosomal Impairment Enhances Cytotoxicity of Fullerenol under Starvation Condition.

Autophagy is well-known as a common cellular response to nanomaterials. As one of the most comprehensively studied carbon-based nanomaterials, fullerene and its derivatives have been reported to bring about autophagic features in various cell lines, but little is known about the role of fullerenol (C60(OH)44) on the modulation of autophagy in human gastric tumor cell line SGC-7901. Fullerenol treatment led to the accumulation of autophagosomes, as evidenced by the increased fluorescent intensity of monodansylcadaverine (MDC) staining cells, an elevated level of LC3 protein, and the observation of auotphagosomes in cytoplasm. Subsequent results of the p62 level demonstrated that the accumulation of autophagosomes resulted from the blockade of autophagic flux rather than the activation of autophagy. Fullerenol disrupted autophagic flux by impairing lysosomal function, including lysosome membrane permeabilization (LMP), alkaline of lysosomes, and reduced activity of capthesin B. Interestingly, fullerenol treatment was noncytotoxic under a nutrient-rich condition. When serum was deprived, cytotoxicity occurred in a concentration- and time-dependent manner, along with massive vacuoles in cytoplasm, a large amount of ROS generation, and finally cell death, which can be ascribed to the disruption of essential autophagy in cells. Taken together, understanding this autophagy-lysosome pathway will shed light on the potential anticancer application of fullerenol.

A LiAlO2/nitrogen-doped hollow carbon spheres (NdHCSs) modified separator for advanced lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries have gained significant attention due to their ultrahigh theoretical specific capacity and energy density. However, their practical commercialization is still facing many intractable problems, of which the most difficult is the shuttle effect of dissolved polysulfides. To restrict the shuttle of polysulfides, herein, a novel double-layer lithium aluminate/nitrogen-doped hollow carbon sphere (LiAlO2/NdHCSs)-modified separator was designed. The upper NdHCSs layer on the separator works as the first barrier to physically and chemically adsorb polysulfides, whereas the bottom LiAlO2 layer acts as the second barrier to physically block the polysulfides without restricting the Li+ transport due to the high ionic conductivity of LiAlO2. Cells with the LiAlO2/NdHCSs-modified separator showed an initial discharge capacity of 1500 mA h g-1 at 0.2C, and a discharge capacity of 543.3 mA h g-1 was obtained after 500 cycles at 2C. Especially, when the areal density of the active material was increased to 4.5 mg cm-2, the cells retained a discharge capacity of 538.6 mA h g-1 after 100 cycles at 0.5C. The outstanding electrochemical performance of Li-S cells with the LiAlO2/NdHCSs-modified separators show a new approach for the applications of Li-S batteries.

Characterization of fullerenol-protein interactions and an extended investigation on cytotoxicity.

Fullerenols, known as polyhydroxylated derivatives of fullerene, have attracted great attention due to their distinctive material properties and potential applications in biology and medicine. As a step toward the elucidation of basic behavior in biological systems, a variety of spectroscopic measurements as well as isothermal titration calorimetry (ITC) were applied to study the interaction between fullerenol (C60(OH)44) and serum proteins (bovine serum albumin (BSA) and γ-globulins). The results of fluorescence spectra indicated that the intrinsic fluorescence of proteins could be effectively quenched by the dynamic mechanism. The affinity values of both proteins bound to fullerenol were of the same order of magnitude. Meanwhile, ITC results showed that the interaction between fullerenol and BSA was enthalpy favorable, while the interaction with γ-globulins was enthalpy unfavorable. Furthermore, fullerenol had little influence on the secondary structure of both proteins. Additional cytotoxicity tests showed that the presence of proteins attenuated the toxic effect of fullerenol on human normal gastric epithelial cell line (GES-1). Thus, the interaction between fullerenol and proteins is indispensable to evaluate the biosafety of fullerenol, which may in turn promotes the development of its biological applications.

Ovalbumin-gum arabic interactions: effect of pH, temperature, salt, biopolymers ratio and total concentration.

The formation of soluble and insoluble complexes between ovalbumin (OVA) and gum arabic (GA) polysaccharide was investigated under specific conditions (pH 1.0-7.0; temperature 4-55 °C; NaCl concentration 0-60mM; total biopolymer concentration 0.05-3.0 wt%) by turbidimetric analysis. For the 2:1 OVA:GA ratio and in the absence of NaCl, soluble and insoluble complexes were observed at pH 4.61 (pHφ1) and 4.18 (pHφ2), respectively, with optimal biopolymer interactions occurring at pH 3.79 (pHopt). Under the same conditions, OVA alone gave only a weak turbidity intensity (turbidity <0.03), whereas GA had none. As the temperature increased, critical pH values shifted toward lower pH, and the maximum turbidity value occurred at 25 °C. The region between pHφ1 and pHφ2 was narrowed and the electrostatic interactions became weaker with increasing NaCl concentration. The maximum turbidity value increased as the total biopolymer concentration increased until reaching a critical value (2.0%), afterwards becoming a constant value.